Anti‐Integrin αvβ6 Autoantibodies Distinguish Ulcerative Colitis From Crohn's Disease With High Diagnostic Accuracy and Outperform ANCA and ASCA Status: A Prospective Cross‐Sectional Study

ABSTRACT Background Reliable biomarkers to distinguish ulcerative colitis (UC) from Crohn's disease (CD) remain limited. Aims To assess the diagnostic accuracy of anti‐integrin αvβ6 autoantibodies for differentiating UC from CD and to compare their performance with anti‐neutrophil cytoplasmic antibodies (ANCA) and anti‐ Saccharomyces cerevisiae antibodies (ASCA). Methods In this prospective cross‐sectional study in patients with UC and CD, serum anti‐integrin αvβ6 autoantibodies, ASCA, and ANCA were measured and clinical data were collected. The primary outcome was the accuracy of anti‐integrin αvβ6 antibodies in distinguishing UC from CD. Secondary analyses compared their performance with ASCA and ANCA status and across IBD subgroups. Results A total of 224 patients were included (UC: n = 106, CD: n = 118, male: 63.8%, median age: 43.5 years). Patients with indeterminate colitis were excluded. At a cut‐off of 2.44 U/mL, anti‐integrin αvβ6 autoantibodies demonstrated a diagnostic accuracy of 86.5%, with a sensitivity of 85.8% and specificity of 87.1%. In a multivariate logistic regression analysis, these autoantibodies were independently associated with UC (OR 36.18, 95% CI 17.0–83.0, p = 4.86 × 10 −19 ) and demonstrated superior diagnostic performance compared to ANCA and ASCA status (Akaike information criterion 184.8 vs. 252.4). Positivity rates followed a gradient across the Montreal classification, increasing from ileal (L1: 7.9%) and ileocolonic (L3: 8.1%) CD towards colonic CD (L2: 43.8%) and UC: 85.8% ( p = 2.04 × 10 −31 ). Conclusions Anti‐integrin αvβ6 autoantibodies demonstrate high diagnostic accuracy and outperform conventional serological markers in distinguishing UC from CD. Importantly, this study provides the first direct comparison with ANCA and ASCA status within the same patient cohort.